Sinus rhythm voltage fingerprinting in patients with mitral valve disease using a high-density epicardial mapping approach.

AIMS: Unipolar voltage (UV) mapping is increasingly used for guiding ablative therapy of atrial fibrillation (AF) as unipolar electrograms (U-EGMs) are independent of electrode orientation and atrial wavefront direction. This study was aimed at constructing individual, high-resolution sinus rhythm (SR) UV fingerprints to identify low-voltage areas and study the effect of AF episodes in patients with mitral valve disease (MVD). METHODS AND RESULTS: Intra-operative epicardial mapping (interelectrode distance 2 mm) of the right and left atrium, Bachmann's bundle (BB), and pulmonary vein area was performed in 67 patients (27 male, 67 ± 11 years) with or without a history of paroxysmal AF (PAF). In all patients, there were considerable regional variations in voltages. UVs at BB were lower in patients with PAF compared with those without [no AF: 4.94 (3.56-5.98) mV, PAF: 3.30 (2.25-4.57) mV, P = 0.006]. A larger number of low-voltage potentials were recorded at BB in the PAF group [no AF: 2.13 (0.52-7.68) %, PAF: 12.86 (3.18-23.59) %, P = 0.001]. In addition, areas with low-voltage potentials were present in all patients, yet we did not find any predilection sites for low-voltage potentials to occur. CONCLUSION: Even in SR, advanced atrial remodelling in MVD patients shows marked inter-individual and regional variation. Low UVs are even present during SR in patients without a history of AF indicating that low UVs should carefully be used as target sites for ablative therapy.

Direction- and rate-dependent fractionation during atrial fibrillation persistence: Unmasking cardiac anisotropy?

This human case is the first to illustrate morphological manifestations of direction- and rate-dependent anisotropic conduction in high-resolution unipolar atrial potentials. Premature impulses induced low-amplitude, fractionated extracellular potentials with exceptionally prolonged durations in a 76-year old longstanding persistent patient with atrial fibrillation (AF), demonstrating direction-dependency of anisotropic conduction. An increased pacing frequency induced presence of similar fractionated potentials, reflecting rate-dependent anisotropy and inhomogeneous, slow conduction. Pacing with different rates and from different sites could aid in identifying nonuniform anisotropic tissue and thus the substrate of AF.

Classification of sinus rhythm single potential morphology in patients with mitral valve disease.

AIMS: The morphology of unipolar single potentials (SPs) contains information on intra-atrial conduction disorders and possibly the substrate underlying atrial fibrillation (AF). This study examined the impact of AF episodes on features of SP morphology during sinus rhythm (SR) in patients with mitral valve disease. METHODS AND RESULTS: Intraoperative epicardial mapping (interelectrode distance 2 mm) of the right and left atrium (RA, LA), Bachmann's bundle (BB), and pulmonary vein area (PVA) was performed in 67 patients (27 male, 67 ± 11 years) with or without a history of paroxysmal AF (PAF). Unipolar SPs were classified according to their differences in relative R- and S-wave amplitude ratios. A clear predominance of S-waves was observed at BB and the RA in both the no AF and PAF groups (BB 88.8% vs. 85.9%, RA 92.1% vs. 85.1%, respectively). Potential voltages at the RA, BB, and PVA were significantly lower in the PAF group (P < 0.001 for each) and were mainly determined by the size of the S-waves amplitudes. The largest difference in S-wave amplitudes was found at BB; the S-wave amplitude was lower in the PAF group [4.08 (2.45-6.13) mV vs. 2.94 (1.40-4.75) mV; P < 0.001]. In addition, conduction velocity (CV) at BB was lower as well [0.97 (0.70-1.21) m/s vs. 0.89 (0.62-1.16) m/s, P < 0.001]. CONCLUSION: Though excitation of the atria during SR is heterogeneously disrupted, a history of AF is characterized by decreased SP amplitudes at BB due to loss of S-wave amplitudes and decreased CV. This suggests that SP morphology could provide additional information on wavefront propagation.

Anatomical hotspots of fractionated electrograms in the left and right atrium: do they exist?

AIMS: Targeting of complex fractionated electrograms (CFEs) in the atria is not yet beneficial in treating drug-refractory atrial fibrillation (AF). In order to gain insight into potential anatomical hotspots of fractionated electrograms, a structured literature search was performed. METHODS AND RESULTS: PubMed was searched for studies describing fractionation during human atrial electrophysiological measurements (n = 565), of which 36 articles described the pre-ablation distribution of fractionated electrograms for the left atrium and/or right atrium in at least four regions. Fractionation was commonly found in high proportions within all regions of both atria, without clear preference for specific regions. Furthermore, no differences in the fractionation distribution between paroxysmal AF and persistent AF patients were observed. CONCLUSION: Whereas atrial inhomogeneous conduction is widely believed to play a key role in AF initiation and perpetuation, different electrophysiological causes for fractionation and the influence of measurement properties complicate identification of the arrhythmogenic substrate. Thereby, simply targeting all CFEs would be short-sighted. Further research is warranted on how to distinguish 'physiologic CFEs' from 'pathologic CFEs', with only the latter reflecting potential targets for ablative therapy of AF.

Benchtop quantification of gutter formation and compression of chimney stent grafts in relation to renal flow in chimney endovascular aneurysm repair and endovascular aneurysm sealing configurations.

BACKGROUND: The chimney technique has been successfully used to treat juxtarenal aortic aneurysms. The two main issues with this technique are gutter formation and chimney graft (CG) compression, which induce a risk for type Ia endoleaks and stent thrombosis, respectively. In this benchtop study, the geometry and renal artery flow of chimney endovascular aneurysm repair configurations were compared with chimney configurations with endovascular aneurysm sealing (ch-EVAS). METHODS: Seven flow phantoms were constructed, including one control and six chimney endovascular aneurysm repairs (Endurant [Medtronic Inc, Minneapolis, Minn] and AFX [Endologix Inc, Irvine, Calif]) or ch-EVAS (Nellix, Endologix) configurations, combined with either balloon-expandable or self-expanding CGs with an intended higher positioning of the right CG in comparison to the left CG. Geometric analysis was based on measurements at three-dimensional computed tomography angiography and included gutter volume and CG compression, quantified by the ratio between maximal and minimal diameter (D-ratio). In addition, renal artery flow was studied in a physiologic flow model and compared with the control. RESULTS: The average gutter volume was 343.5 ± 142.0 mm3, with the lowest gutter volume in the EVAS-Viabahn (W. L. Gore & Associates, Flagstaff, Ariz) combination (102.6 mm3) and the largest in the AFX-Advanta V12 (Atrium Medical Corporation, Hudson, NH) configuration (559.6 mm3). The maximum D-ratio was larger in self-expanding CGs than in balloon-expandable CGs in all configurations (2.02 ± 0.34 vs 1.39 ± 0.13). The CG compression had minimal influence on renal volumetric flow (right, 390.7 ± 29.4 mL/min vs 455.1 mL/min; left, 423.9 ± 28.3 mL/min vs 410.0 mL/min in the control). CONCLUSIONS: This study showed that gutter volume was lowest in ch-EVAS in combination with a Viabahn CG. CG compression was lower in configurations with the Advanta V12 than with Viabahn. Renal flow is unrestricted by CG compression.

Characterization of pre-existing arrhythmogenic substrate associated with de novo early and late postoperative atrial fibrillation.

BACKGROUND: PoAF is the most common complication after cardiac surgery and may occur in patients with pre-existing arrhythmogenic substrate. Characterization of this substrate could aid in identifying patients at risk for PoAF. We therefore compared intra-atrial conduction parameters and electrogram morphology between patients without and with early- (≤5 days after surgery) and late- (up to 5 years) postoperative atrial fibrillation (PoAF). METHODS AND RESULTS: Epicardial mapping of the right and left atrium and Bachmann's Bundle (BB) was performed during sinus rhythm (SR) in 263 patients (207male, 67 ± 11 years). Unipolar potentials were classified as single, short or long double and fractionated potentials. Unipolar voltage, fractionation delay (time difference between the first and last deflection), conduction velocity (CV) and conduction block (CB) prevalence were measured. Comparing patients without (N = 166) and with PoAF (N = 97), PoAF was associated with lower CV and more CB at BB. Unipolar voltages were lower and more low-voltage areas were found at the left and right atrium and BB in PoAF patients. These differences were more pronounced in patients with late-PoAF (6%), which could even occur up to 5 years after surgery. Although several electrophysiological parameters were related to PoAF, age was the only independent predictor. CONCLUSIONS: Patients with de novo PoAF have more extensive arrhythmogenic substrate prior to cardiac surgery compared to those who remained in SR, which is even more pronounced in late-PoAF patients. Future studies should evaluate whether intra-operative electrophysiological examination enables identification of patients at risk for developing PoAF and hence (preventive) therapy.

Detection of Endo-epicardial Asynchrony in the Atrial Wall Using One-Sided Unipolar and Bipolar Electrograms.

Endo-epicardial asynchrony (EEA) is a new mechanism possibly maintaining atrial fibrillation. We aimed to determine the sensitivity and best recording modus to detect EEA on electrograms recorded from one atrial side using electrogram fractionation. Simultaneously obtained right atrial endo- and epicardial electrograms from 22 patients demonstrating EEA were selected. Unipolar and (converted) bipolar electrograms were analyzed for presence and characteristics of fractionation corresponding to EEA. Sensitivity of presence of EEA corresponding fractionation was high in patients (86-96%) and moderately high (65-78%) for the asynchronous surface area for unipolar and bipolar electrograms equally. In bipolar electrograms, signal-to-noise ratio of EEA corresponding fractionation decreased and additional fractionation increased for electrograms recorded at the endocardium. Sensitivity of fractionation corresponding to EEA is high for both unipolar and bipolar electrograms. Unipolar electrograms are more suited for detection of EEA due to a larger signal-to-noise ratio and less disturbance of additional fractionation. Unipolar electrograms are more suited than bipolar electrograms to detect endo-epicardial asynchrony on one side of the atrial wall using electrogram fractionation.

Daily Supplementation of L-Glutamine in Atrial Fibrillation Patients: The Effect on Heat Shock Proteins and Metabolites.

Pharmaco-therapeutic strategies of atrial fibrillation (AF) are moderately effective and do not prevent AF onset and progression. Therefore, there is an urgent need to develop novel therapies. Previous studies revealed heat shock protein (HSP)-inducing compounds to mitigate AF onset and progression. Such an HSP inducing compound is L-glutamine. In the current study we investigate the effect of L-glutamine supplementation on serum HSP27 and HSP70 levels and metabolite levels in patients with AF patients (n = 21). Hereto, HSP27 and HSP70 levels were determined by ELISAs and metabolites with LC-mass spectrometry. HSP27 levels significantly decreased after 3-months of L-glutamine supplementation [540.39 (250.97-1315.63) to 380.69 (185.68-915.03), p = 0.004] and normalized to baseline levels after 6-months of L-glutamine supplementation [634.96 (139.57-3103.61), p < 0.001]. For HSP70, levels decreased after 3-months of L-glutamine supplementation [548.86 (31.50-1564.51) to 353.65 (110.58-752.50), p = 0.045] and remained low after 6-months of L-glutamine supplementation [309.30 (118.29-1744.19), p = 0.517]. Patients with high HSP27 levels at baseline showed normalization of several metabolites related to the carbohydrates, nucleotides, amino acids, vitamins and cofactors metabolic pathways after 3-months L-glutamine supplementation. In conclusion, L-glutamine supplementation reduces the serum levels of HSP27 and HSP70 within 3-months and normalizes metabolite levels. This knowledge may fuel future clinical studies on L-glutamine to improve cardioprotective effects that may attenuate AF episodes.

Atrial fibrillation fingerprinting; spotting bio-electrical markers to early recognize atrial fibrillation by the use of a bottom-up approach (AFFIP): Rationale and design.

BACKGROUND: The exact pathophysiology of atrial fibrillation (AF) remains incompletely understood and treatment of AF is associated with high recurrence rates. Persistence of AF is rooted in the presence of electropathology, defined as complex electrical conduction disorders caused by structural damage of atrial tissue. The atrial fibrillation fingerprinting (AFFIP) study aims to characterize electropathology, enabling development of a novel diagnostic instrument to predict AF onset and early progression. HYPOTHESES: History of AF, development of post-operative AF, age, gender, underlying heart disease, and other clinical characteristics impact the degree of electropathology. METHODS: This study is a prospective observational study with a planned duration of 48 months. Three study groups are defined: (1) patients with (longstanding) persistent AF, (2) patients with paroxysmal AF, and (3) patients without a history of AF, all undergoing open-chest cardiac surgery. Intra-operative high-resolution epicardial mapping is performed to identify the patient-specific electrical profile, whereas the patient-specific biological profile is assessed by evaluating proteostasis markers in blood samples and atrial appendage tissue samples. Post-operative continuous rhythm monitoring is performed for detection of early post-operative AF. Late post-operative AF (during 5-year follow-up) is documented by either electrocardiogram or 24-hour Holter registration. RESULTS: The required sample size for this study is estimated at 447 patients. Up till now, 105 patients were included, of whom 36 have a history of AF. CONCLUSION: The AFFIP study will elucidate whether electrophysiological and structural characteristics represent a novel diagnostic tool, the AF fingerprint, to predict onset and early progression of AF in cardiac surgery patients.

The Impact of Filter Settings on Morphology of Unipolar Fibrillation Potentials.

Using unipolar atrial electrogram morphology as guidance for ablative therapy is regaining interest. Although standardly used in clinical practice during ablative therapy, the impact of filter settings on morphology of unipolar AF potentials is unknown. Thirty different filters were applied to 2,557,045 high-resolution epicardial AF potentials recorded from ten patients. Deflections with slope ≤ - 0.05 mV/ms and amplitude ≥ 0.3 mV were marked. High-pass filtering decreased the number of detected potentials, deflection amplitude, and percentage of fractionated potentials (≥ 2 deflections) as well as fractionation delay time (FDT) and increased percentage of single potentials. Low-pass filtering decreased the number of potentials, percentage of fractionated potentials, whereas deflection amplitude, percentage of single potentials, and FDT increased. Notch filtering (50 Hz) decreased the number of potentials and deflection amplitude, whereas the percentage of complex fractionated potentials (≥ 3 deflections) increased. Filtering significantly impacted morphology of unipolar fibrillation potentials, becoming a potential source of error in identification of ablative targets. Graphical Abstract Impact of filtering on morphology of unipolar AF potentials. High-pass, low-pass and notch filters were applied to 2,557,045 high-resolution epicardial AF potentials recorded from ten patients. Filtering significantly impacted AF potential morphology, i.e., number of detected potentials, peak-to-peak amplitude, number of deflections, and fractionation delay time. CFP, complex fractionated potential (≥ 3 deflections); DP, double potential (two deflections); FDT, fractionation delay time; SP, single potential (one deflection).

The impact of obesity on early postoperative atrial fibrillation burden.

BACKGROUND: Obesity has been linked to the development of postoperative atrial fibrillation. This study is aimed at investigating the role of body mass index in the evolution of de novo, early postoperative atrial fibrillation by assessing differences between obese and nonobese patients undergoing cardiac surgery. METHODS: Patients with early de novo postoperative atrial fibrillation were included. Continuous cardiac rhythms were recorded during the first 5 postoperative days in obese (N = 67, 66 ± 9 years; 51 [76%] male) and nonobese (N = 89, 69 ± 9; 75 [84%] male) patients without a history of atrial fibrillation undergoing cardiac surgery. Postoperative atrial fibrillation burden was defined as the ratio between total duration of all atrial fibrillation episodes and total recording time (atrial fibrillation burden, %). RESULTS: A total of 1191 (median: 5/patient) postoperative atrial fibrillation episodes were identified in the obese group compared with 1218 (median: 4/patient) in the nonobese group. The median duration and number of prolonged (>60 minutes) postoperative atrial fibrillation episodes were higher in obese patients (250 vs 145 minutes, P = .003, and median of 2 vs 1 episode, P = .031). Obesity was associated with a larger early postoperative atrial fibrillation burden (obese patients: median, 7%; interquartile range, 2.5-19.7 vs nonobese patients: median, 3.2%; interquartile range, 0.5-8.8, P = .001) mainly on the third postoperative day (P = .021). CONCLUSIONS: Obesity predisposes to a larger number of prolonged atrial fibrillation episodes in the early postoperative period after cardiac surgery for coronary artery disease or valvular heart disease. The higher atrial fibrillation burden in the early postoperative period occurred particularly on the third day. Future studies will determine whether obesity prevention may play a key role in reducing the incidence of postoperative atrial fibrillation in patients undergoing cardiac surgery.

Unipolar atrial electrogram morphology from an epicardial and endocardial perspective.

BACKGROUND: Endo-epicardial asynchrony (EEA) and the interplay between the endocardial and epicardial layers could be important in the pathophysiology of atrial arrhythmias. The morphologic differences between epicardial and endocardial atrial electrograms have not yet been described, and electrogram morphology may hold information about the presence of EEA. OBJECTIVE: The purpose of this study was to directly compare epicardial to endocardial unipolar electrogram morphology during sinus rhythm (SR) and to evaluate whether EEA contributes to electrogram fractionation by correlating fractionation to spatial activation patterns. METHODS: In 26 patients undergoing cardiac surgery, unipolar electrograms were simultaneously recorded from the epicardium and endocardium at the inferior, middle, and superior right atrial (RA) free wall during SR. Potentials were analyzed for epi-endocardial differences in local activation time, voltage, RS ratio, and fractionation. The surrounding and opposite electrograms of fractionated deflections were evaluated for corresponding local activation times in order to determine whether fractionation originated from EEA. RESULTS: The superior RA was predisposed to delayed activation, EEA, and fractionation. Both epicardial and endocardial electrograms demonstrated an S-predominance. Fractionation was mostly similar between the 2 sides; however, incidentally deflections up to 4 mV on 1 side could be absent on the other side. Remote activation was responsible for most fractionated deflections (95%) in SR, of which 4% could be attributed to EEA. CONCLUSION: Local epi-endocardial differences in electrogram fractionation occur occasionally during SR but will likely increase during arrhythmias due to increasing EEA and (functional) conduction disorders. Electrogram fractionation can originate from EEA, and this study demonstrated that unipolar electrogram fractionation can potentially identify EEA.